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Biomedical subjects

A Magrini

Publications and source records attributed to A Magrini.

At least 19 recordsLinked to original sources
PubMed2006

ACP1 and offspring sex ratio in smoking puerperae: a study at population level.

BACKGROUND: Data from previous study by our group suggest that in smoking women sex ratio of offspring is higher in newborns carrying ACP1C allele than in other ACP1 genotypes, suggesting that differences observed among human population concerning the effect of smoking may depend in part on this genetic factor. OBJECTIVES: In order to further explore this issue we have studied another population and have analysed the relationship between sex ratio and ACP1C gene frequency at population level. METHODS: The analysis includes 719 consecutive births from Central Italy considered in a previous paper and 5510 consecutive births from Sardinia. Data from English and Japanese populations have also been considered in the analysis. RESULTS: Among newborns not carrying ACP1C there is a decrease of SR among the offspring of smoking mothers, while among newborns carrying the ACP1C allele there is an increase of SR among the offspring of smoking mothers relative to non-smoking mothers. Considering Sardinian, Italian, English and Japanese population there is a linear positive relationship between C allele frequency and SR in smoking mothers. CONCLUSIONS: The present observation suggests an interaction between smoking and ACP1 regarding their effects on sex ratio, by which the presence of the ACP1C allele appears to counteract the effect of smoking. This suggests that genetic background may modify the effects of toxic environmental factors on gamete production and functionality and/or on intrauterine survival.

Adult↗
PubMed2006

Helicobacter pylori eradication and l-dopa absorption in patients with PD and motor fluctuations.

OBJECTIVE: To investigate if Helicobacter pylori (HP) eradication could make an effective and long-lasting improvement in the pharmacokinetic and clinical response to l-dopa in patients with Parkinson disease (PD) and motor fluctuations. METHODS: In a group of 34 HP-infected, motor-fluctuating patients with PD, the short-term (1-week) and long-term (3-month) beneficial effect of HP eradication (n = 17) was investigated in a double-blind fashion in comparison with a generic antioxidant treatment (n = 17), by means of pharmacokinetic, clinical, and gastrointestinal assessments. Results were compared with placebo treatment. RESULTS: Differently from the antioxidant-treated patients, the HP-eradicated patients showed a significant increase of l-dopa absorption, which was coupled with a significant improvement of clinical disability and with a prolonged "on-time" duration, whereas gastritis/duodenitis scores significantly decreased in line with a better l-dopa pharmacokinetics. CONCLUSIONS: These data demonstrate a reversible Helicobacter pylori (HP)-induced interference with l-dopa clinical response related to the impaired drug absorption, probably due to active gastroduodenitis. Therefore, the authors suggest that HP eradication may improve the clinical status of infected patients with Parkinson disease and motor fluctuations by modifying l-dopa pharmacokinetics.

Aged↗
PubMed2006

NMR exposure sensitizes tumor cells to apoptosis.

NMR technology has dramatically contributed to the revolution of image diagnostic. NMR apparatuses use combinations of microwaves over a homogeneous strong (1 Tesla) static magnetic field. We had previously shown that low intensity (0.3-66 mT) static magnetic fields deeply affect apoptosis in a Ca2+ dependent fashion (Fanelli et al., 1999 FASEBJ., 13;95-102). The rationale of the present study is to examine whether exposure to the static magnetic fields of NMR can affect apoptosis induced on reporter tumor cells of haematopoietic origin. The impressive result was the strong increase (1.8-2.5 fold) of damage-induced apoptosis by NMR. This potentiation is due to cytosolic Ca2+ overload consequent to NMR-promoted Ca2+ influx, since it is prevented by intracellular (BAPTA-AM) and extracellular (EGTA) Ca2+ chelation or by inhibition of plasma membrane L-type Ca2+ channels. Three-days follow up of treated cultures shows that NMR decrease long term cell survival, thus increasing the efficiency of cytocidal treatments. Importantly, mononuclear white blood cells are not sensitised to apoptosis by NMR, showing that NMR may increase the differential cytotoxicity of antitumor drugs on tumor vs normal cells. This strong, differential potentiating effect of NMR on tumor cell apoptosis may have important implications, being in fact a possible adjuvant for antitumor therapies.

Apoptosis↗
PubMed2006

Dust in the underground railway tunnels of an Italian town.

This article assesses hazards associated with exposure to dust in tunnels and platforms of the A and B lines of Rome's underground railway and provides an informed opinion on the risks to workers and the travelling public of exposure to tunnel dust. The study focused on the analysis and measurement of dust granulometric classes PM10, respirable fraction, respirable combustible dust, and the organic, metallic, siliceous, and fibrous components. Comparing the measurement values from the tunnels and platforms with those found at the entrances to the underground railway stations, it emerges that dust concentration in the tunnels and platforms is three times higher, with a maximum PM10 value of 479 microg/m3. Averaged over 24 hours, in relation to the above ground levels, drivers and station staff are exposed to an additional value of 11 microg/m3 and 10 microg/m3, respectively. If commuters were to remain in the trains or on the station platforms, the 24-hour average exposure would increase by 3 microg/m3. Iron and silica were the major components found in the dust. The use of silica sand in the emergency braking system of the carriages is capable of causing a dispersion of quartz in the air in percentages varying from 5% to 14%. Methods are suggested in this article for the reduction of dust dispersion.

Air Pollutants↗
PubMed2006

Shift work increases the frequency of duodenal ulcer in H pylori infected workers.

AIM: To evaluate whether shift work is associated with an increased rate of peptic ulcer in H pylori infected workers. METHODS: During a two year period, consecutive dyspeptic workers underwent non-invasive evaluation of H pylori status by means of urea 13C breath test or stool testing. Those testing positive were included in the study and divided into two main categories: day-time workers and shift workers. An upper gastrointestinal endoscopy was performed in all workers, and biopsy specimens were taken from the stomach to confirm the presence of H pylori infection (culture and histology). RESULTS: A total of 247 day-time workers and 101 shift workers were included. The prevalence of duodenal ulcer was significantly higher in shift workers than in day-time workers (29 of 101 v 23 of 247; OR = 3.92, 95% CI 2.13 to 7.21), and persisted after multivariate analysis, taking into account possible confounding factors (OR = 3.96, 95% CI 2.10 to 7.47). CONCLUSION: Shift work increases the ulcerogenic potential of H pylori infection and should be considered a risk factor for duodenal ulcer in infected shift workers. Treatment of infection in this high risk group may improve the health of workers and may reduce the economic impact of peptic ulcer.

Adult↗
PubMed2005

Oxidative Bax dimerization promotes its translocation to mitochondria independently of apoptosis.

Bax is a cytosolic protein, which in response to stressing apoptotic stimuli, is activated and translocates to mitochondria, thus initiating the intrinsic apoptotic pathway. In spite of many studies and the importance of the issue, the molecular mechanisms that trigger Bax translocation are still obscure. We show by computer simulation that the two cysteine residues of Bax may form disulfide bridges, producing conformational changes that favor Bax translocation. Oxidative, nonapoptogenic treatments produce an up-shift of Bax migration compatible with homodimerization, which is reverted by reducing agents; this is accompanied by translocation to mitochondria. Dimers also appear in pure cytosolic fractions of cell lysates treated with H2O2, showing that Bax dimerization may take place in the cytosol. Bax dimer-enriched lysates support Bax translocation to isolated mitochondria much more efficiently than untreated lysates, indicating that dimerization may promote Bax translocation. The absence of apoptosis in our system allows the demonstration that Bax moves because of oxidations, even in the absence of apoptosis. This provides the first evidence that Bax dimerization and translocation respond to oxidative stimuli, suggesting a novel role for Bax as a sensor of redox imbalance.

Apoptosis↗
PubMed2005

Helicobacter pylori duodenal colonization is a strong risk factor for the development of duodenal ulcer.

AIM: To test the hypothesis that duodenal colonization represents the final crucial step in the development of Helicobacter pylori related duodenal ulcer. METHODS: Patients with non-ulcer dyspepsia who had gastric colonization by H. pylori were included in the study. At baseline endoscopy, we evaluated the prevalence of duodenal colonization (culture, urease testing and histology), and cytotoxin-associated gene A status (polymerase chain reaction). No patients received eradication during 1 year follow-up. At this time, endoscopy was repeated and the incidence of duodenal ulcer was assessed. RESULTS: Among 181 patients completing follow-up, 53 (29%) had duodenal colonization: 72% of them were cytotoxin-associated gene A positive, versus 37% patients without duodenal colonization (P < 0.001). Duodenal ulcer developed in 12 (22.6%) patients with duodenal colonization and in two (1.6%) without duodenal colonization (odds ratio for duodenal ulcer: 6.29, 95% confidence intervals 2.44-17.45). The incidence of duodenal ulcer was similar among cytotoxin-associated gene A positive and cytotoxin-associated gene A negative subjects with duodenal colonization: 21.05% versus 26.6%. CONCLUSIONS: The assessment of duodenal colonization by H. pylori in patients with non-ulcer dyspepsia is strongly predictive for the subsequent development of duodenal ulcer and may help to stratify patients at risk for this disease.

Duodenal Ulcer↗
PubMed2005

Serum glucose concentration and ACP1 genotype in healthy adult subjects.

Acid phosphatase locus 1 (ACP 1 ) or cytosolic low molecular weight protein tyrosine phosphatase is a polymorphic enzyme that can hydrolyze phosphotyrosine-containing peptides of the human insulin receptor and of band 3 protein. High-activity ACP 1 may favor an increase in serum glucose concentration through a depression of insulin action and through inactivation of aldolase, phosphofructokinase, and glyceraldehyde-3-phosphate dehydrogenase induced by dephosphorylation of band 3 protein. In diabetic subjects, we have previously reported lower serum glucose concentration in subjects with low-activity ACP 1 A and AB phenotypes. We have now studied the relationship between serum glucose concentration and ACP 1 genotype in a sample of 137 healthy adult workers of our university. In males, serum glucose concentration is significantly higher in medium-high- than in low-activity ACP 1 genotypes. With advancing age in males, there is a progressive increase in glycemic differential between medium-high- and low-activity ACP 1 genotypes. The data suggest that normal variability of ACP 1 genotype influences serum glucose concentration in normal individuals. Such influence depends on sex and in males becomes more marked with advancing age.

Adult↗
PubMed2004

CagA-positive Helicobacter pylori strains may influence the natural history of atherosclerotic stroke.

OBJECTIVE: To test the hypothesis that infection with virulent cytotoxin-associated gene-A (CagA)-bearing Helicobacter pylori strains influences the atherosclerotic process and the clinical course in atherosclerotic stroke patients. METHODS: ELISA was used to assess the seroprevalence of infection by H. pylori and CagA-positive strains in 185 patients. Intima-media thickness (IMT) was determined by Doppler ultrasound. Baseline, 1-week, and 1-month NIH Stroke Scale (NIHSS) scores were used to evaluate the short-term clinical course. RESULTS: H. pylori infection was found in 79% of patients; 58% of these tested positive for CagA. IMT was higher among CagA-positive patients than among CagA-negative ones (1.13 +/- 0.26 mm vs 0.97 +/- 0.15 mm; univariate analysis, p = 0.0001; multivariate analysis, odds ratio [OR], 2.36; 95% CI, 1.57 to 3.54; p = 0.0001) or H. pylori-negative ones (1.01 +/- 0.17 mm; univariate analysis, p = 0.007; multivariate analysis, OR, 1.90; 95% CI, 1.22 to 2.97; p = 0.005). CagA-positive patients had poorer initial outcomes based on serial measurements of the NIHSS score (repeated measures analysis of variance, p < 0.0001). No significant difference in IMT and NIHSS score was found between H. pylori-positive and H. pylori-negative patients. CONCLUSIONS: Infection with cytotoxin-associated gene-A-positive Helicobacter pylori strains in atherosclerotic stroke patients is associated with greater intima-media thickness and poorer short-term outcome compared with cytotoxin-associated gene-A-negative patients.

Aged↗
PubMed2004

Maternal cigarette smoking, metabolic enzyme polymorphism, and developmental events in the early stages of extrauterine life.

The recent observation that maternal ACP1 genotype has an interactive effect with smoking on intrauterine development prompted us to search for a possible interaction effect between smoking and ACP1 genotype on haptoglobin (Hp) development in the neonatal period. ACP1 is a highly polymorphic protein tyrosine phosphatase involved in signal transduction of several growth factor receptors. The enzyme is composed of two isoforms, F and S. We studied 299 infants born in the Department of Obstetrics of the University Hospital of Rome La Sapienza. We found that an interaction between ACP1 genotype and smoking has an effect on haptoglobin development: A significant delay of haptoglobin development in infants born to smoking mothers is observed only in infants with the ACP1 *B/*B genotype, which shows the highest concentration of the ACP1 F isoform. The results indicate that the ACP1 genotype modifies the deleterious effects of smoking on development not only during intrauterine life but also during the early stage of extrauterine life.

Female↗
PubMed2003

Cross-sectional and longitudinal evaluation of uterine artery Doppler velocimetry for the prediction of pre-eclampsia in normotensive women with specific risk factors.

OBJECTIVE: To evaluate the performance, in the prediction of pre-eclampsia, of (1) an abnormal mean uterine artery resistance index (RI; cross-sectional index) at 24 weeks of gestation, (2) the individual longitudinal flow pattern of results observed at 16, 20 and 24 weeks of gestation and (3) a multiple logistic regression model including the individual longitudinal flow pattern and the mean RI at 24 weeks. METHODS: A total of 144 normotensive pregnant women with risk factors for pre-eclampsia were evaluated with uterine artery color Doppler at 16, 20 and 24 weeks' gestation. The following indices were obtained: (1) cross-sectional index: the mean RI of both uterine arteries at 24 weeks' gestation was calculated for each patient and considered abnormal when >/= 0.58; (2) longitudinal indices: the individual longitudinal flow pattern of mean RI of both the main uterine arteries at 16, 20 and 24 weeks' gestation was derived for each subject and defined as (a) the typical physiological flow pattern, with a trend of decrease in values or (b) the non-physiological flow pattern. The probability of having a pregnancy complicated by pre-eclampsia was also calculated by means of a multivariate logit model. The log-odds was modeled as a function of variables related to maternal characteristics, the individual longitudinal flow pattern indicator, and of the mean RI at 24 weeks' gestation as a continuous variable. RESULTS: Pregnancies had a physiological course in 108 (75%) women, while 36 (25%) women developed pre-eclampsia during the third trimester. For the prediction of pre-eclampsia, the use of an abnormal uterine artery RI index (> or = 0.58) at 24 weeks showed a sensitivity of 77.8%, a specificity of 67.6%, a positive predictive value (PPV) of 44.4% and a negative predictive value (NPV) of 90.1%, with a likelihood ratio (LR) for an abnormal test of 2.4; with the longitudinal flow pattern indicator, sensitivity was 88.9%, specificity 82.4%, PPV 62.7% and NPV 95.7%, with a LR for an abnormal test of 4.9; the use of a logit model yielded a sensitivity of 72.2%, a specificity of 90.7%, a PPV of 72.2% and a NPV of 90.7%, with a LR for an abnormal test of 8.0. CONCLUSIONS: In this study the use of an individual longitudinal flow pattern indicator resulted in improving accuracy in the prediction of pre-eclampsia as compared with the traditional cross-sectional mean RI at 24 weeks. A further increase in specificity and PPV was obtained using a logit model that includes the longitudinal flow pattern indicator and the cross-sectional RI at 24 weeks. Since both the longitudinal flow pattern indicator and the logit model showed a high performance in predicting pre-eclampsia in women with risk factors for impaired placentation, they might be used to identify a high-risk population in which preventive measures and/or therapeutic options might be tested.

Adult↗
PubMed2003

Hypoxic stress stably alters apoptotic parameters on U937 cells.

Tumor promonocytic U937 cells cultured under a low O(2)/high CO(2) atmosphere display altered characteristics after restoration of normal atmosphere: increased resistance to apoptosis induced by different treatments; apoptotic morphology; lack of glutathione (GSH) extrusion in apoptosis; lack of protection by antioxidants; and lack of Ca(2+) mobilization with thapsigargin. These alterations were stably maintained for many months of culture in normal conditions, originating the stable U937-HX variant. Since the hypoxic treatment did not produce a great selective pressure, the alterations are conceivably the result of stable adaptative response.

Antioxidants↗
PubMed2003

Apoptotic GSH extrusion is associated with free radical generation.

Reactive oxygen species (ROS) are involved in many forms of apoptosis and mediate apoptosis in a number of cell types. In this paper, we use a variant of U937 monocytic cells (U937 HX) that show different biochemical features with respect to standard U937. Apoptotic standard U937 extrude reduced glutathione (GSH) and generate free radicals concomitantly with loss of mitochondria transmembrane potential (mt Deltapsi). These events are correlated with the extrusion of intracellular GSH. Conversely, apoptotic U937 HX cells retain GSH, and the loss of mt Deltapsi is not accompanied by generation of free radicals. The perfect inverse correlation between (a) ROS generation and (b) the presence of intracellular GSH during apoptosis suggests novel mechanisms to finely tune ROS generation in apoptosis.

Apoptosis↗
PubMed2002

Smoking and the genetics of signal transduction: an association study on retinopathy in type 1 diabetes.

BACKGROUND: Recent studies suggest a complex association between smoking and retinopathy that probably depends on the interaction between many variables. We have reported an association between ACP1 phenotype and retinopathy in type 1 diabetes. Additionally, the deleterious effects of smoking on intrauterine growth are dependent on ACP1, a low-molecular-weight tyrosine phosphatase that modifies signal transduction. We examine here the interaction between smoking and ACP1 as a mediator of susceptibility to diabetic retinopathy in a sample of puerperae with type 1 diabetes. SUBJECTS AND METHODS: Seventy-eight women who had just delivered live infants were studied. ACP1 phenotype was determined by starch gel electrophoresis. Three-way contingency tables were analyzed. RESULTS: There is a significant epistatic interaction between smoking and ACP1 phenotype concerning their effects on retinopathy. In subjects with low ACP1 activity, frequency of retinopathy was slightly higher in smokers than in nonsmokers. However, in subjects with medium-high ACP1 activity, frequency of retinopathy was significantly lower in smokers than in nonsmokers. A logistic regression analysis using retinopathy as the dependent variable revealed that smoking, ACP1, and ACP1 by smoking interaction, as well as the interaction between smoking and age of the women, are the most robust predictors of retinopathy. CONCLUSIONS: The effect of smoking on retinopathy in women with type 1 diabetes depends on many variables, which supports the hypothesis of complex interactions between smoking and other variables in the pathogenesis of this disease. Variability of genetic factors involved in signal transduction may affect endothelium proliferation through the regulation of growth factors and through regulation of glycemic levels. Because cigarette smoke influences signal transduction, its impact on diabetic retinopathy may be mediated by ACP1.

Adult↗
PubMed2001

Isozymes of Ipomoea batatas catechol oxidase differ in catalase-like activity.

The amino acid sequences of two isozymes of catechol oxidase from sweet potatoes (Ipomoea batatas) were determined by Edman degradation of BrCN cleavage fragments of the native protein and by sequencing of amplified cDNA fragments. Sequence alignment and phylogenetic analysis of plant catechol oxidases revealed about 80% equidistance between the two I. batatas catechol oxidases and approximately 40--60% to catechol oxidases of other plants. When H(2)O(2) was applied as substrate the 39 kDa isozyme, but not the 40 kDa isozyme, showed catalase-like activity. The structure of the 40 kDa isozyme was modeled on the basis of the published crystal structure of the 39 kDa isozyme [T. Klabunde et al., Nat. Struct. Biol. 5 (1998) 1084]. The active site model closely resembled that of the 39 kDa isozyme determined by crystallography, except for a mutation of Thr243 (40 kDa isozyme) to Ile241 (39 kDa isozyme) close to the dimetal center. This residue difference affects the orientation of the Glu238/236 residue, which is thought to be responsible for the catalase-like activity of the 39 kDa isozyme for which a catalytic mechanism is proposed.

Amino Acid Sequence↗
PubMed2000

Infection with Helicobacter pylori and leukocyte response in patients with myocardial infarction.

To test whether Helicobacter pylori may contribute to the inflammatory response following myocardial infarction, the levels of IgG antibodies to Helicobacter pylori and some parameters of leukocyte activity were measured in 63 patients and 61 comparable controls. Helicobacter pylori-positive patients showed a significantly higher expression of the adhesion molecule LFA-1 on neutrophils than Helicobacter pylori-negative patients (433+/-29.0 vs. 398.8+/-38.9 mean fluorescence channels; P<0.0001), whereas no significant difference for any parameters tested was found in control subjects. These data suggest a role of Helicobacter pylori in inducing a leukocyte response following myocardial infarction.

Aged↗